KIDNEY IMPLICATIONS OF THE INITIAL ESTIMATED GLOMERULAR FILTRATION RATE RESPONSE TO SODIUM GLUCOSE COTRANSPORTER-2 INHIBITION WITH EMPAGLIFLOZIN; THE ‘ESTIMATED GLOMERULAR FILTRATION RATE DIP’ IN EMPA-REG OUTCOME

M D’EMDEN1, B J KRAUS2,3, M R. WEIR4, G L. BAKRIS5, M MATTHEUS6, D Z.I. CHERNEY7, N SATTAR8, H J.L.  HEERSPINK9, I RITTER10, M VON EYNATTEN10, B ZINMAN11, S E.  INZUCCHI12, C WANNER13, A KOITKA-WEBER2,10,13

1Department of Endocrinology, Royal Brisbane and Women’s Hospital, Brisbane, Australia, 2Department of Internal Medicine I, University Hospital Würzburg, Würzburg, Germany, 3Comprehensive Heart Failure Centre, University of Würzburg, Würzburg, Germany, 4Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, USA, 5Department of Medicine, Am. Heart Assoc. Comprehensive Hypertension Center, University of Chicago Medicine, Chicago, USA, 6Boehringer Ingelheim Pharma GmbH & Co.KG, Ingelheim, Germany, 7Department of Medicine and Department of Physiology, Division of Nephrology, University Health Network, University of Toronto, Toronto, Canada, 8Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK, 9Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands, 10Boehringer Ingelheim International GmbH, Ingelheim, Germany, 11Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, and University of Toronto, Toronto, Canada, 12Section of Endocrinology, Yale University School of Medicine, New Haven, USA, 13Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia

Aim: We investigated whether estimated glomerular filtration rate (eGFR) dip after empagliflozin (EMPA) initiation was influenced by baseline characteristics and/or impacted EMPA-induced risk reduction in kidney outcomes.
Background: EMPA reduces cardiovascular and kidney risk in type 2 diabetes (T2D) patients with cardiovascular disease (CVD). EMPA induces an initial ‘dip’ in mean eGFR.
Methods: In EMPA-REG OUTCOME, patients received EMPA 10mg, 25mg or placebo (PBO). ‘eGFR dip’ >10% impact on risk reduction with EMPA for incident or worsening nephropathy was assessed in 6,668 participants.
Results: ‘eGFR dip’ >10% from baseline at Week 4 occurred in 28.3% participants on EMPA vs. 13.4% on PBO. An eGFR decline >30% occurred in 1.4% and 0.9%, respectively. EMPA participants with an ‘eGFR dip’ >10% were older, had longer diabetes duration and showed higher KDIGO (Kidney Disease: Improving Global Outcomes) risk category. The odds ratio [OR; 95%CI] for an ‘eGFR dip’ with EMPA vs. PBO was 2.7 [2.3–3.0]. Baseline diuretic use and/or higher KDIGO risk category were predictive of an ‘eGFR dip’ in EMPA vs. PBO. In subgroups based on these factors with an OR for dipping below (or equal) vs. above this overall OR, beneficial effects with EMPA on kidney outcomes were consistent. ‘eGFR dip’ didn’t affect risk reduction for primary kidney outcome. Acute renal failure rates were lower or similar in EMPA vs. PBO, regardless of baseline predictive factors for an ‘eGFR dip’.
Conclusions: T2D patients with advanced kidney disease and/or on diuretic therapy at baseline were more likely to have an initial ‘eGFR dip’ >10% with EMPA. EMPA treatment was safe and associated with improved kidney outcomes, regardless of baseline predictive factors or such initial ‘eGFR dip’.


Biography:
Michael d’Emden graduated from University of Tasmania in 1978. He was a resident and registrar at the Princess Alexandra Hospital in Brisbane before moving to Royal Melbourne Hospital in 1983. He obtained his fellowship in 1985 and completed a PhD at University of Melbourne in 1988. He undertook post-doctoral studies at the University of Iowa, USA for two years before taking up his current position at the Royal Brisbane & Womens Hospital in 1990, where he is now Director of Endocrinology and Diabetes. His major clinical interests are diabetes and lipid metabolism.

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